血脑屏障（BBB）损伤是创伤性脑外伤后中枢神经系统二次损伤的主要原因，是创伤性脑外伤治疗的难点所在。新近研究发现膜联蛋白A2能够调控“连接复合体”的分布、表达进而调控血管内皮细胞紧密性。我们预实验发现：Anxa2-/-小鼠在受控皮质冲击手术模型后，血脑屏障损伤程度加重；在原代人脑微血管内皮细胞上，给予重组膜联蛋白A2能够逆转缺氧和IL-1β造成的细胞间渗漏；分子水平上，膜联蛋白A2能够抑制损伤诱导的Robo4-paxillin-ARF6激活；这些预实验结果初步提示：膜联蛋白A2很可能参与创伤性脑外伤后BBB功能损伤的过程，并且和Robo4-paxillin-ARF6通路相关。据此，本课题拟从动物、细胞、分子水平等多层次明确膜联蛋白A2在创伤性脑外伤后BBB功能损伤中的作用并阐明其分子机制。为预防、治疗创伤性脑外伤后BBB功能失调造成的二次损伤提供新的思路和新的靶点。

Disruption in blood-brain barrier (BBB) integrity is widely considered to be the primary vascular event after TBI. Hence, finding novel vascular targets that can protect the BBB should be an important therapeutic approach. Annexin A2 (A2) is a Ca2+-dependent anionic phospholipid and membrane-binding protein. We previously found A2 may be a key factor in vascular structure and functional development. Our pilot data demonstrate that when subjected to TBI, Anxa2-/- mice suffered more severe BBB disruption compared to WT mice. Annexin A2 could inhibit activation of ARF6 by promoting formation of Robo4-paxillin complex, which protect brain vascular endothelial cell integrity. Based on these studies, we assess the hypothesis that Annexin A2 contributes to regulation of BBB function, and therefore exogenous rA2 can in fact be used as a novel therapeutic approach to protect the BBB and improve outcomes after TBI. These results may provide translational hope that protection on the BBB in TBI patients might also lead to improved clinical outcomes.